Background The underlying mechanism of choroidal neovascularization(CNV) is multifactorial and complex.Focal adhesion kinase(FAK) plays a crucial role in controlling essential cellular processes and influencing distinct steps of the angiogenic response.But to our knowledge,seldom study on the effect of FAK on CNV formation has been reported previously.Objective In this study,the effect of several CNV risk factors on the expression of FAK in cultured retinal pigment epithelium(RPE) cells was investigated to illuminate effect of FAK on CNV.Methods Human RPE cells were isolated from donor eyes and exposed to H2O2,swallow of outer segment of photoreceptors(POS) and extracellular matrix(ECM) separately with the treating as follows:RPE cells were co-cultured with 10,20,50 and 100μmol/L H2O2 for 20 days;POS(1×106/ml) were co-cultivated with RPE cells for 20 days(setting control group,POS group,hypoxia group with 200μmol/L CoCl2,and POS+hyoxia group);RPE cells were cultured on the plates coated with 100mg/L fibronectin(FN),laminin(LN) or collagen typeⅠfor 30minutes or 1 hour.The expression of FAK and pFAK in RPE cells were examined by Western blot analysis.Results FAK was highly expressed in the 20μmol/L and 50μmol/L H2O2 groups compared with control group(P＜0.01);while he expression level of pFAK was reduced after treated with H2O2 in comparison with the control group(P＜0.01).After cultured with POS for 20 days,the undigested lysosome could be observed in RPE cells.The expressions of FAK and pFAK in RPE cells were not significantly changed between control group and POS groups(P＞0.05),but those in hypoxia group were significantly up-regulated in comparison with control group(P＜0.01).Compared with the hypoxia group,the expression amount of pFAK was elevated in POS+hyoxia group(P＜0.01).In comparison with control group,the increased pFAK expression was seen in FN,LN and collagen typeⅠtreating for 1-hour groups(P＜0.05,P＜0.01).Conclusion FAK pathway participates in several CNV-initiated signaling,such as H2O2,POS and ECM,in cultured RPE cells.It is reasonable to believe that FAK potentially plays an important role in CNV-dependent disorder.

To investigate the anticancer effects of ring C in 18β-glycyrrhetinic acid (GA), a series of GA derivatives featured with 9(11)-ene moiety in ring C were designed and synthesized. The structures were confirmed by IR, LC-MS and 1H NMR. Their inhibitory effects towards human prostate cancer PC-3 and leukemia HL-60 cell lines were determined. Most of the derivatives displayed stronger antiproliferative activities than GA. Particularly, compound 14 showed promising anticancer activity with the GI50 values of 4.48 µmol · L(-1) and 1.2 µmol · L(-1) against PC-3 and HL-60 cells respectively, which is worth further study.
Antineoplastic Agents ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Drug Design ; Glycyrrhetinic Acid ; analogs & derivatives ; chemistry ; HL-60 Cells ; drug effects ; Humans ; Male ; Prostatic Neoplasms ; pathology

Objective To observe the motions of the rectum and bladder by image?guided radiotherapy ( IGRT) and to analyze their impact on treatment. Methods Eighteen patients with prostate cancer undergoing intensity?modulated radiotherapy ( IMRT) were enrolled in the study and 247 cone?beam computed tomography ( CBCT) images were obtained from this study. The clinical target volume, bladder, and rectum were contoured on all simulated CT and CBCT to examine their volume and position changes. The dose distributions were recalculated based on the data of the x?, y?, and z?axis setup errors. The doses to planning target volume ( PTV) and organs at risk were calculated in the replanning, and their impact on treatment was analyzed. Comparison of the planning and replanning results was made by paired t?test. The effects of displacements and volumes of the bladder and rectum on target doses were analyzed by Pearson correlation method. Results Great changes in the volumes of the bladder and rectum were observed during the treatment. For the planning and replanning results, PTVD95% was 7777. 37 cGy vs. 7628. 56 cGy ( P=0. 027), PTV Dmin was 87. 91 cGy vs. 83. 35 cGy (P=0. 000), and RVP was 5. 89% vs. 8. 31%(P=0. 000). There were correlations between PTVD95% and the motions of the bladder and rectum, with correlation coefficients of 0. 296 and 0. 177, respectively. The correlation coefficient between rectal volume and PTVD95% was 0. 115, indicating a certain correlation. There is a certain correlation between and PTV Dmin and bladder volume, with a correlation coefficient of?0. 128. Conclusions The recovery of the state during localization for the bladder and rectum, especially the latter, has great significance to ensure the target dose and reduce exposure of the rectum in the IMRT for prostate cancer.

Objective To analyze the data from intensity-modulated radiotherapy ( IMRT) for prostate cancer guided by kilovoltage cone-beam computed tomography (CBCT), and to provide a clinical basis for selecting the optimal image registration method and reasonable target volume margins.Methods A total of 16 patients with prostate cancer who received radical IMRT were enrolled, and CBCT for online position verification was performed 214 times.The images were obtained after conventional skin marking and laser alignment, and automatic registration, bone registration, soft tissue registration, and manual registration were performed for CBCT images and planned CT images.The differences between these four registration methods were evaluated, and the margins for extending clinical target volume into planning target volume (PTV) were calculated.Results The setup errors in left-right, anterior-posterior, and cranial-caudal directions for automatic registration, bone registration, soft tissue registration, and manual registration were-0.6±2.8 mm/-0.6±4.5 mm/-0.6±3.8 mm,-0.7±2.7 mm/-0.9±4.5 mm/-0.8±4.1 mm,-0.8± 2.6 mm/-0.3±4.4 mm/-1.1±4.0 mm, and-0.6±2.9 mm/-0.7±5.1 mm/-0.9±3.9 mm, respectively. There were no significant differences between the four registration methods.The margins for extension in the left-right, anterior-posterior, and cranial-caudal directions were calculated as 4.7 mm, 5.2 mm, and 6.5 mm, respectively.Conclusions With a comprehensive consideration of various factors, a default setting of automatic registration and manual fine adjustment is appropriate for CBCT-guided radiotherapy for prostate cancer.The margins for extension in the left-right, anterior-posterior, and cranial-caudal directions are 4.7 mm, 5.2 mm, and 6.5 mm, respectively.

Objective To evaluate the clinical efficacy and toxicity of intensity-modulated radiation therapy (IMRT) following prostatectomy for elderly patients with prostate cancer.Methods Ninety-eight prostate cancer patients receiving IMRT after prostatectomy were included in this study.The median age was 68 years old.The number of patients with low-,middle-and high-risk prostate cancer was 10,21 and 67,respectively.Two patients had oligometastases (pelvic bone metastases).Sixty-four patients were treated with IMRT combined with endocrine therapy.Among them,43 cases received adjuvant volumetric modulated arc therapy (VMAT),and 55 patients received salvage IMRT.The median radiotherapy dose was 72 Gy for the tumor bed.Twenty-nine patients received radiotherapy of the pelvic node region with a median dose of 50 Gy.Results The median follow-up time was 40 months.The 5-year overall survival (OS),biochemical recurrence-free survival (BRFS) and local control (LC) were 90％,76％ and 100％,respectively.The OS (88.8％ vs.90.8％,P=0.94),BRFS (75.9％ vs.71％,P=0.79) or LC (100％ vs.100％,P=0.32) did not significantly differ between the adjuvant and salvage radiotherapy groups,respectively.The incidence of grade Ⅰ-Ⅱ late rectal toxicities was 24.1％,and no ≥ grade 3 late toxicity was observed.The incidence of grade 1-2 late bladder toxicities was 29.9％,and 3.4％ for grade 3.Conclusion IMRT following prostatectomy yields high clinical efficacy and slight late toxicities in elderly patients with prostate cancer.

OBJECTIVETo investigate the relationship between various Chinese medicine (CM) types and T-cell subsets (CD4(+) and CD8(+)) in the colonic mucous membranes of patients with ulcerative colitis (UC).

METHODSFifty UC patients were enrolled, after differentiation into four types by CM syndromes, i.e., the internal heat-damp accumulation type (IHDA), the qi-stagnancy with blood stasis type (QSBS), the Pi-Shen yang-deficiency type (PSYD) and the yin-blood deficiency type (YBD). From every patient, 3-5 pieces of intestinal mucous membrane tissues were taken through colonoscopy to determine the levels of the T-cell subsets (CD4(+) and CD8(+)) using immunohistochemical method. The results were compared with those in the normal control.

RESULTSThe level of CD8(+)increased and the ratio of CD4(+)/CD8(+)decreased mainly in colonic mucous membranous tissues in UC patients. The level of CD4(+)decreased significantly in IHDA types (P<0.01), but decreased only slightly in the PSYD, QSBS and YBD types. CD8(+)increased significantly in the IHDA types (P<0.01), but only slightly in the other three types.

CONCLUSIONThe IHDA types of UC are closely related with T-cell subsets. The difference of T-cell subsets in various IHDA types of UC patients has provided a theoretical basis for syndrome differentiation in the CM typing of UC.

Adolescent ; Adult ; Aged ; Biopsy ; Blood Circulation ; CD4-CD8 Ratio ; Colitis, Ulcerative ; immunology ; pathology ; Colon ; drug effects ; immunology ; pathology ; Colonoscopy ; Female ; Humans ; Immunohistochemistry ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Qi ; T-Lymphocyte Subsets ; drug effects ; Yang Deficiency ; immunology ; pathology ; Yin Deficiency ; immunology ; pathology ; Young Adult

Background: There have been few reports of mutations in the beta-myosin heavy chain(MYH7)gene in hypertrophic cardiomyopathy(HCM),which is associated with sudden cardiac death caused by HCM.This study aimed to screen the mutation sites in the sarcomeric gene MYH7 in Chinese patients with HCM.We also p1anned to analyze the pathogenicity of the mutation site as well as its significance in clinical and forensic medicine.Methods: From January 2006 to June 2017,autopsy cases were collected from the Department of Pathology,the Affiliated Hospital of Qingdao University.The experiment was to detect MYH7 gene status in formalin-fixed paraffin-embedded tissues from 18 independent autopsy cases who suffered HCM related sudden death(fatal HCM)and 20 cases without cardiomyopathy.Common mutation exon fragments of MYH7 gene were amplified by polymerase chain reaction.The end-of-deoxygenation method and gene cloning method were further performed to analyze the mutation sites.Homologous comparison among mutant sites was conducted using BLAST online database.Results:The 1336th nucleotide of MYH7 gene at exon 14 was converted from T to G in one HCM case,resulting in the conversion of threonine(Thr)at position 446 to proline(Pro).In another case,the 1402th nucleotide at exon 14 was converted from T to C,resulting in the conversion of phenylalanine(Phe)at position 468 to leucine(Leu).Homologous comparison results showed that the two amino acid residues of Thr446 and Phe468 are highly conserved among different species.Conclusions: Our results showed fatal HCM harbored mutations of Thr446Pro and Phe468Leu in the MYH7 gene.It is significant for clinical and forensic medicine to further explore the functions and detailed mechanisms of these mutations.

This paper explored the curative effect of combined modality therapy and extended field radiotherapy for early-stage Hodgkin's Lymphoma. 104 cases of early-stage Hodgkin's Lymphoma from Jan 1987 to Dec 2010 in PLA Hospital 307 were retrospectively analyzed, including 76 cases in combined modality therapy group and 28 cases in extended field radiotherapy group, and the long-term efficacy and toxicity of two therapy modalities were evaluated. The results showed that the median survival time of 104 cases was 85.42 months, the complete remission rates of combined modality therapy and extended field radiotherapy groups were 72.4 and 71.4 respectively (P = 0.924); the overall response rates of combined modality therapy and extended field radiotherapy groups were 97.4 and 96.4 respectively (P = 0.779); the 5-year overall survival (OS) rates in the 2 groups were 89.5 and 89.1 respectively, and the 8-year OS rates of the 2 groups were 81.3 and 70.6. No statistical difference was found in above-mentioned 2 groups. Moreover, the 5-year progression free survival (PFS) rates of these 2 groups were 84.2 and 69.0 (P = 0.04), and 8-year PFS rates of these 2 groups were 80.0 and 55.5 (P = 0.04) respectively, the 5-year relapse rates of these 2 groups were 28.1 and 45.6 (P = 0.023) respectively. It is concluded that the combined modality therapy can raise the PFS rate and reduce the relapse rate as compared with extended field radiotherapy for early-stage Hodgkin's Lymphoma, but there is no difference in the overall survival rate between the 2 groups.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; Child ; Combined Modality Therapy ; Female ; Hodgkin Disease ; drug therapy ; radiotherapy ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult

OBJECTIVETo study the influence of male age on the outcome of conventional IVF-ET.

METHODSBased on male age, 170 couples undergoing conventional IVF-ET were divided into three groups: <35 yr (n = 60), 35 -39 yr (n = 77) and > or = 40 yr (n = 33). We observed the rates of fertilization, cleavage, good quality embryo, implantation, clinical pregnancy and abortion in different groups.

RESULTSThere were no significant differences among the three groups in semen volume ([3.10 +/- 1.22] ml vs [2.84 +/- 1.05] ml vs [2.80 +/- 0.79] ml), sperm concentration ([54.23 +/- 26.07] x 10(6)/ml vs [60.27 +/- 24.80] x 10(6)/ml vs [60.21 +/- 27.42] x 10(6)/ml) and sperm viability ([53.93 +/- 13.25]% vs [56.10 +/- 16.58]% vs [51.82 +/- 15.45]%) (P>0.05). The men of the > or = 40 yr group showed a significantly lower percentage of grade a + b sperm ([40.97 +/- 11.91]%) than those of the <35 and 35 - 39 yr groups ([48.47 +/- 11.78]% and [46.84 +/- 13.51]%) (P<0.05), and morphologically normal sperm ([11.76 +/- 5.97]%) than those of the <35 yr group ([15.25 +/- 6.94]% (P<0.05). The rates of fertilization, cleavage, good quality embryo, implantation, clinical pregnancy were 81.52%, 82.61%, 52.33%, 18.06% and 33.33% in the > or = 40 yr group, with no significant differences from those of the <35 yr group (83.18%, 82.68%, 56.99%, 22.40% and 40.00%) and the 35 - 39 yr group (78.78%, 80.66%, 55.01%, 21.74% and 38.96%) (P>0.05), while the abortion rate was markedly increased in the > or = 40 yr group as compared with the <35 yr group (36.36% vs 8.33%, P>0.05).

CONCLUSIONIncreasing male age is related with decreasing percentages of progressively motile sperm and morphologically normal sperm, but not obviously with the rates of fertilization, good quality embryo, implantation, pregnancy and abortion.

Adult ; Age Factors ; Female ; Fertilization in Vitro ; Humans ; Male ; Middle Aged ; Paternal Age ; Pregnancy ; Pregnancy Outcome

OBJECTIVETo explore the correlation of males'age with sperm apoptosis, sperm DNA integrity and other seminal parameters.

METHODSWe collected 104 semen samples and divided them into three groups according to the males' age: <35 yr (n = 43), 35 -39 yr (n = 31), and > or = 40 yr (n = 30). Based on the WHO Laboratory Manual (4th ed), we detected the seminal parameters, calculated the percentage of apoptotic sperm by flow cytometry (FCM), determined sperm DNA integrity by Acridine orange staining, and compared the results among the three groups.

RESULTSThere were no statistically significant differences among the < 35 yr, 35 -39 yr and > or = 40 yr groups in semen volume ([2.87 +/- 0.89] ml vs [2.98 +/- 1.09] ml vs [2.65 +/- 0.95] ml), sperm concentration ([60.40 +/- 25.43] x 10(6)/ml vs [69.74 +/- 28.33] x 10(6)/ml vs [55.97 +/- 27.22] x 10(6)/ml) (P>0.05). The percentage of progressively motile sperm was significantly lower in the > or = 40 yr ([39.00 +/- 8.35 %) than in the <35 and 35 -39 yr groups ([48.73 +/- 9.89]% and [45.65 +/- 10.55]%) (P<.0.1), and so was the percentage of morphologically normal sperm in the > or = 40 yr than in the < 35 yr group ([11.11 +/- 8.26]% vs [16.43 +/- 8.75 ]%, P<0.01). The percentage of apoptotic sperm was markedly higher in the > or = 40 yr than in the <35 yr group ([11.82 +/- 5.77]% vs [7.04 +/- 3.50]%, P<0.01), while the sperm DNA integrity significantly reduced in the > or = 40 yr group ([75.52 +/- 10.60]%) as compared with the <35 yr ([86.55 +/- 5.60])% and 35 -39 yr group ( [81.39 +/- 8.94]%) (P<0.01). The males' age was correlated positively with the rate of sperm apoptosis (P<0.01), and negatively with sperm DNA integrity and the percentage of progressively motile sperm (P<0.01).

CONCLUSIONThe advance in males' age increases sperm apoptosis and reduces sperm progressive motility, normal morphology and DNA integrity.

Adult ; Age Factors ; Apoptosis ; genetics ; DNA ; Flow Cytometry ; Humans ; Infertility, Male ; genetics ; Male ; Sperm Count ; Sperm Motility ; Spermatozoa ; cytology